We have confirmed that hydrogen sulfide (H 2 S) is a possible relaxation factor in the rat bladder, and H 2 S-induced bladder relaxation is impaired in 18-week-old (18W) spontaneously hypertensive rats (SHRs), which show bladder dysfunctions. We compared effects of NaHS and GYY4137 (H 2 S donors) on bladder contractility and micturition reflex, and H 2 S contents and expression of enzymes related to H 2 S biosynthesis (CBS, MPST and CAT) in the bladder between 12W and 18W male SHRs. Effects of NaHS (1×10-8 to 3×10-4 M) were evaluated on carbachol (10-5 M)induced pre-contracted bladder strips. Under urethane-anesthesia, effects of intravesically instilled GYY4137 (10-8 to 10-6 M) on the rat micturition reflex were examined. The H 2 S contents and expression of CBS, MPST and CAT were measured by methylene blue method and western botting. Compared to 12W SHRs, NaHS-induced maximal relaxation of bladder strips was significantly decreased, GYY4137-induced intercontraction intervals prolongation was attenuated, the bladder H 2 S content and expression level of CBS, MPST and CAT in the bladder dome was higher in 18W SHRs. These results indicate that H 2 S-induced bladder relaxation in SHRs is impaired time-dependently, suggesting that early intervention in SHRs with H 2 S donors may prevent the development of hypertension-mediated bladder dysfunctions.

No abstract

It was reported that temporal changes in severity of ischemic brain injury, but the mechanism is mostly unknown. In ischemic hippocampus, extracellular Zn 2+ accumulates in neurons, resulting in neuron death. Excitatory amino acid carrier (EAAC) 1 reduces zinc toxicity. Here, we examined the involvement of EAAC1 in temporal changes in ischemic zinc toxicity.[Methods] Mice (12 weeks) were subjected to ischemia at 09:00 (ZT4) or 23:00 (ZT18). At 72 h after, zinc accumulation was assessed by Zn 2+ probe, TSQ, and the number of neurons were examined by immunostaining. Diurnal changes in hippocampal EAAC1 expression were assessed by western blot. Mice were subjected to ischemia at ZT18 after an EAAC1 inhibitor, TBOA, injection (i.c.v.) and we examined zinc accumulation and the number of neurons.[Results] Ischemia induced TSQ(+) cells in hippocampus and the number of TSQ(+) cells were less at ZT18 than ZT4. Compared to ZT4, a decrease in neuron death were observed at ZT18. EAAC1 expression was higher at ZT18 than ZT4. Besides, TBOA increased TSQ(+) cells and decreased neuron death at ZT18.[Conclusion] These results suggest temporal changes in severity of ischemic neuronal damage might be mediated by zinc accumulation via diurnal variation of EAAC1 expression.